We have, over the past several years, successfully combined the various methodologies described (radioactive isotope pulse-labeling, operant behavior technics and brain perfusion). Although we have reported minute to minute changes in putative transmitter (NE) disposition in perfusate, as related to operant schedule changes and drug administration, we have not as yet examined the effects of more than one schedule of reinforcement nor the problem of where the transmitter candidates "come" from. Utilization of trace amounts of high specific activity precursors will allow a more certain evaluation regarding the source (dopamine from dopaminergic neurones, 5-HT from serotonergic neurones, etc. rather than a non-specific effect or from extracellular sources). In addition, our data on environmental factors which significantly reverse behavioral consequences of psychoactive drugs suggest that this may be a means of separating peripheral effects of drugs, which in turn alter behavior through stimulus consequences of autonomic reactivity, from direct central action. An examination of neurochemical consequences to environmental manipulation will likewise be undertaken. Preliminary data on social hierarchy and acute and chronic morphine administration and withdrawal from morphine indicates that "aggression" or other more subtle forms of agonistic behavior are sensitive not only to acute morphine administration but withdrawal from much lower doses of morphine that have been used in the past to induce fighting. We will explore those variables that tend to control and modify this social-operant behavior and test the effects of various transmitter synthesis and metabolic inhibitors upon the biochemical-psychopharmacology of tolerance and dependence.